What medication should be substituted for triamterene (Triamterene)-HCTZ (Hydrochlorothiazide) in a 64-year-old female patient with impaired renal function (decreased eGFR) who is also taking Losartan (Angiotensin II receptor blocker) 100 mg daily?

Medication Substitution for Triamterene-HCTZ in a Patient with Medication-Induced Kidney Injury

A calcium channel blocker (CCB) such as amlodipine should be substituted for triamterene-HCTZ in this patient with medication-induced kidney injury who is already on losartan. 1, 2, 3

Rationale for Discontinuing Triamterene-HCTZ

1. Current Medication Issues:

   • The patient has experienced a significant decline in eGFR (from 80 to 51) after starting triamterene-HCTZ one month ago
   • Triamterene is specifically contraindicated in patients with significant kidney dysfunction (eGFR <45 mL/min) 1, 4
   • The combination of losartan (an ARB) with triamterene (potassium-sparing diuretic) increases the risk of hyperkalemia 1
   • Triamterene has been reported to cause irreversible renal failure in some cases 5

2. Drug Interactions:

   • The current regimen creates a "triple whammy" effect on the kidneys:
     • ARB (losartan) affects efferent arteriolar tone
     • Diuretic (HCTZ) reduces intravascular volume
     • Potassium-sparing component (triamterene) can accumulate in renal impairment

Recommended Substitution: Amlodipine

Primary Recommendation:

• Amlodipine 2.5-5 mg daily 2, 3

Rationale for Amlodipine:

• Dihydropyridine CCBs are potassium-neutral and do not worsen renal function 2, 3
• Amlodipine has demonstrated efficacy and safety in patients with renal dysfunction 3
• Amlodipine does not accumulate in patients with renal impairment 3
• The combination of an ARB (losartan) with a CCB provides complementary mechanisms of action for BP control 1, 2
• Starting dose should be 2.5 mg daily with potential titration to 5 mg based on BP response and tolerability 2, 3

Alternative Options (If CCB Not Suitable):

1. Loop Diuretic Option:

   • Furosemide 20-40 mg daily or torsemide 5-10 mg daily 1
   • Preferred over thiazides in patients with moderate renal dysfunction (eGFR <30 mL/min) 1
   • Does not have the potassium-sparing effects that can worsen hyperkalemia when combined with losartan

2. ACE Inhibitor Option (Replacing Both Current Medications):

   • Not recommended in this specific case as the patient is already on an ARB (losartan)
   • Combining ACE inhibitors and ARBs is potentially harmful 1

Monitoring Recommendations:

• Check serum potassium and renal function within 1-2 weeks after medication change 2
• Monitor blood pressure response at 1 month 2
• Reassess renal function after 3 months to confirm improvement or stabilization 2
• If using amlodipine, monitor for peripheral edema, especially in female patients 2

Important Considerations:

• The decline in eGFR from 80 to 51 represents a significant medication-induced kidney injury that requires prompt intervention
• Avoid all potassium-sparing agents in this patient with impaired renal function who is already on an ARB 1, 4
• Ramipril has shown renoprotective effects compared to amlodipine in some studies 6, but cannot be used with losartan
• High-dose losartan (100 mg) may cause initial decline in eGFR but has long-term benefits for heart failure outcomes 7

By substituting amlodipine for triamterene-HCTZ, you can maintain blood pressure control while allowing renal function to recover and avoiding the risk of hyperkalemia in this patient.